Inhibition of hamster adrenal 11 beta/19-hydroxylase activity.
Increased mineralocorticoid activity has been associated with elevated urinary levels of 19-nordeoxycorticosterone in several forms of experimental and human hypertension. Biosynthesis of 19-norsteroids involves hydroxylation of the C-19 methyl group. We synthesized the 4-hydroxy analogs of deoxycorticosterone, deoxycorticosterone acetate, progesterone, and androstenedione and evaluated them as inhibitors of deoxycorticosterone 11 beta/19-hydroxylase using hamster adrenal mitochondrial preparations. These 4-hydroxy analogs were inhibitors of this P 450 hydroxylase, with approximately 10 times weaker affinity than their respective natural substrates. 4-Hydroxydeoxycorticosterone was the most potent inhibitor evaluated in this study. The half-maximal inhibitory concentration of deoxycorticosterone hydroxylation was 5 microM, 15 microM, more than 50 microM, and 14 microM, respectively, for the above compounds.
Johnston
J O
JO
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Weintraub
P M
PM
Melby
J C
JC
D000311:Adrenal Glands / Q000201:enzymology*; D000818:Animals; D006224:Cricetinae; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D008928:Mitochondria / Q000201:enzymology; D015394:Molecular Structure; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000494:pharmacology
D013256:Steroids; D013250:Steroid Hydroxylases; C027110:steroid 19-hydroxylase